Oak Ridge (ip-192.com): A petascale supercomputer built by Cray at Oak Ridge National Laboratory (ORNL) was necessary to study enzymes moving at the molecular level and perform hundreds of chemical processes that have ripple effects necessary for life. Previously, protein complexes were viewed as static entities with biological function understood in terms of direct interactions, but that isn't the case.
"Our discovery is allowing us to perhaps find the knobs that we can use to improve the catalytic rate of enzymes and perform a host of functions more efficiently," said Pratul Agarwal, a member of the Department of Energy laboratory's 
Computer Science and Mathematics Division. The researchers found that enzymes have similar features that are entirely preserved from the smallest living organism - bacteria - to complex life forms, including humans.
"If something is important for function, then it will be present in the protein performing the same function across different species," Agarwal said. "For example, regardless of which company makes a car, they all have wheels and brakes."
Similarly, scientists have known for decades that certain structural features of the enzyme are also preserved because of their important function. Agarwal and fellow scientist Arvind Ramanathan believe the same is true for enzyme flexibility.
"The importance of the structure of enzymes has been known for more than 100 years, but only recently have we started to understand that the internal motions may be the missing piece of the puzzle to understand how enzymes work," Agarwal said. "If we think of the tree as the model, the protein move at the molecular level with the side-chain and residues being the leaves and the protein backbone being the entire stem."
This paper, titled "Evolutionarily conserved linkage between enzyme fold, flexibility and catalysis," was first published in PLoS Biology and may have wide reaching implications. Agarwal believes the research could lead to medicines targeting hard to cure diseases such as AIDS and help to produce cheaper biofuls.
This illustration provides a representation for the internal motions coupled to the catalytic step of the enzyme Cyclophilin A. The substrate bound at the active site is shown in cyan sticks and the highly flexible regions in the enzyme are highlighted in a tube-like representation. The transparent tubes indicate the directionality of the motion. The colors on the tube indicate the extent to which these regions move, with red and blue regions representing maximum and minimum mobility, respectively.
Hydrogen bond interactions from the surface of the enzyme connect all the way to the active site and are indicated as yellow dashes. The interactions and the internal motions in Cyclophilin A are conserved from bacteria to humans. Illustration: Oak Ridge National Laboratory
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